Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

Ronald D. Seidel; Zohra Merazga; Dharma Raj Thapa; Jonathan Soriano; Emily Spaulding; Ahmet S. Vakkasoglu; Paige Ruthardt; Wynona Bautista; Steven N. Quayle; Peter A. Kiener; Simon Low; John F. Ross; Saso Cemerski; Anish Suri; Steven C. Almo; Rodolfo J. Chaparro

doi:10.1038/s41598-021-98716-z

Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

Ronald D. Seidel, Zohra Merazga, Dharma Raj Thapa, Jonathan Soriano, Emily Spaulding, Ahmet S. Vakkasoglu, Paige Ruthardt, Wynona Bautista, Steven N. Quayle, Peter A. Kiener, Simon Low, John F. Ross, Saso Cemerski, Anish Suri, Steven C. Almo, Rodolfo J. Chaparro

Biochemistry

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.

Original language	English (US)
Article number	19220
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-98716-z
State	Published - Dec 2021

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Seidel, R. D., Merazga, Z., Thapa, D. R., Soriano, J., Spaulding, E., Vakkasoglu, A. S., Ruthardt, P., Bautista, W., Quayle, S. N., Kiener, P. A., Low, S., Ross, J. F., Cemerski, S., Suri, A., Almo, S. C., & Chaparro, R. J. (2021). Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells. Scientific reports, 11(1), Article 19220. https://doi.org/10.1038/s41598-021-98716-z

Seidel, RD, Merazga, Z, Thapa, DR, Soriano, J, Spaulding, E, Vakkasoglu, AS, Ruthardt, P, Bautista, W, Quayle, SN, Kiener, PA, Low, S, Ross, JF, Cemerski, S, Suri, A, Almo, SC & Chaparro, RJ 2021, 'Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells', Scientific reports, vol. 11, no. 1, 19220. https://doi.org/10.1038/s41598-021-98716-z

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abstract = "Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.",

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AU - Seidel, Ronald D.

AU - Merazga, Zohra

AU - Thapa, Dharma Raj

AU - Soriano, Jonathan

AU - Spaulding, Emily

AU - Vakkasoglu, Ahmet S.

AU - Ruthardt, Paige

AU - Bautista, Wynona

AU - Quayle, Steven N.

AU - Kiener, Peter A.

AU - Low, Simon

AU - Ross, John F.

AU - Cemerski, Saso

AU - Suri, Anish

AU - Almo, Steven C.

AU - Chaparro, Rodolfo J.

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Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

Abstract

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